The speed and extent of COVID-19 pandemic, caused by the SARS-CoV2 virus, have created unprecedented devastations and challenges. It is now well-established that timely and accurate diagnosis is essential to taming this pandemic. Unlike PCR based tests, which can only diagnose active infections, serological diagnosis of anti- viral antibodies can establish prior infections. Therefore, accurate and efficient serology tests will be important not only for establishing disease prevalence, but also for understanding immunity, testing vaccines efficacy and monitoring disease resurgence. Fortunately, SARS-CoV2 antibodies can be detected using well-established immunoassay formats such as ELISA, ECLIA and CMIA. However, the enormous demand for diagnostic tests is creating unprecedented shortage of otherwise routine reagents and the workforce needed to carry out these tests. Given these headwinds, it will not only be helpful, but in fact crucial, to find potential ways to increase the availability, reduce the complexity and improve the throughput of serological assays in order to meet the projected 5 million daily testing capacity needed by our nation. Our company, in collaboration with our academic partners and with support from NIBIB, has developed and commercialized various novel protein engineering and conjugation technologies that can improve immunoassays. In particular, we have developed more sensitive and robust ELISA and homogenous immunoassays through the use of photoreactive antibody-binding domains (pAbBDs). These small protein adapters can rapidly and site-specifically label antibodies to allow efficient antibody conjugation and immobilization. Since pAbBDs can be produced at large scale, they can also serve as a covalent-binding and highly specific IgG/IgM detecting agent in lieu of secondary antibodies, which are comparatively expensive and complex to produce. Antibodies can be directly labeled with pAbBDs in serum, which eliminates an incubation and wash step required with standard ELISA and significantly reduces assay variability and time. In addition, our previously developed recombinant protein modification technique, termed STEPL (Sortase-Tag Expressed Protein Ligation), will allow recombinant viral antigens to be easily ligated with a chemical tag, and subsequently be site-specifically and covalently immobilized onto a microplate surface, which will lead to improved antibody capture capacity and assay sensitivity. Taken together, these innovations can help both improve existing ELISA- based assays and also enable the creation of novel homogenous serology tests. In collaboration with the Hospital of University of Pennsylvania?s clinical laboratory, we will adapt and rapidly implement our technologies to combat COVID-19 using the methods outlined below: Aim 1. Create ?single-wash? SARS-CoV2 ELISA serology assay using pAbBD as IgG/IgM detecting agent; Aim 2. Develop highly sensitive, ?no-blocking? and ?reusable? SARS-CoV2 ELISA serology assay through site-specific and covalent immobilization of antigens; Aim 3: Develop pAbBD constructs for use in ?mix-and-read? homogeneous anti-viral antibody assays.